1. Field of the Invention
The present invention relates to novel compounds, salts thereof and use thereof as an effective ingredient for preventing and curing dementias and more particularly, a senile dementia.
2. Related Arts
In recent years, medical techniques have great advanced to prolong the average span of human life and as a result, senile dementias tend to increase. As typical senile dementias, there are a cerebral vascular dementia due to a cerebral infarction, hemorrhage or the like and an Alzheimer Type dementia, cause of which has been estimated as an atrophy or falling off of cerebral nerve cells. Symptoms of such senile dementias mainly appear as a retention defect, orientation defect or thinking disturbance, and emotional disturbance and abnormal behavior may be observed as concerned symptoms.
The Alzheimer type dementia tends to increase, as number of aged peoples of 65 years old or more increases in total population and thus it becomes one of social problems requiring urgent countermeasures including an inquiry of cause, establishment of positive remedy, various matters in a family caring for the patient. According to pathological and biochemical studies, this type dementia has possibly caused by a falling off of cerebral nerve cells, cerebral atrophy, defect on acetylcholine and other nervous conducting substances or accumulation of amyloid-.beta.-protein in brain. Among them, the study on acetylcholine disturbance is most advanced, but real state is under study and an excellent curing agent and therapeutics have not been found.
In recent years, THA (1,2,8,4-tetrahydro-9-aminoacridine) was developed in USA, as an agent for curing the Alzheimer type dementia, to give a topic with great interests. However, recent news report that an effectiveness and a certain side effect of THA were called in question.
Therefore, it was anxious to develop such an agent for preventing and curing dementias that its pharmacological ef-fects ensurely appear and has low toxicity.
Starting from the development of said THA, developments on anti-dementia agents have been proceeded in various countries in the world and main current thereof lies in developing an agent for activating acetylcholinic nervous conducting substances. There are 3 strategies for activating acetylcholinic nervous conducting functions.
Namely, the first measure is an exhibition of acetylcholine esterass to increase a concentration of acetylcholine decreased in brain, second is an acceleration of acetylcholine discharge in synapse, and third is a binding with an acetylcholine receptor to actuate the receptor.
Said THA shows an inhibition to acetylchotine esterass but its action cannot be said as powerful. At the present time, the main current in the development lies in providing a substance for actuating muscarinic acetylcholine receptors, based on the third strategy, which has been studied by various laboratories. There are 2 muscarinic acetylcholine receptors in brain, namely muscarine 1 receptor and muscarine 2 receptor and it has been reported that actuation of muscarine 1 shows higher activity than that of muscarine 2 ["J. Med. Chem.", Vol. 34, page 1086 (1991); "J. Med. Chem.", Vol. 35, page 1280 (1992); "J. Med. Chem.", Vol. 35, page 2274 (1992), Jap. Pat. No. Sho 61 (A.D. 1986) - 280497(A) and Jap. Pat. No. Hei 2 (A.D. 1990) -36183(A)].
The compounds according to the present invention, as shown later, has 1-azabicyclo[3.3.0]octane ring. In Jap. Pat. No. Hei 3 (A.D. 1991) - 38272, there are disclosed compounds with such a ring and analogous skeleton, including following compound, but the official gazette doe not refer to an actuation activity of muscarinic acetylcholine receptor. ##STR2##